Nobel Prizes that Followed

Following close to three decades of amazing discoveries on the cell cycle, several of the major researchers received Nobel Prizes for their work.

In 2001, Tim Hunt along with Paul Nurse and Lee Hartwell received the Nobel Prize in Physiology or Medicine “for their discoveries of key regulators of the cell cycle” (Nobel Prize, 2001). Lee Hartwell first identified the cdc genes which direct much of the cell cycle. Paul Nurse built on the work of Hartwell, further outlining the role of particular genes involved in the cell cycle. Finally, Tim Hunt discovered one of the key molecular features of the cell cycle, cyclins.

In 2004, Avram Hershko, Irwin Rose, and Aaron Ciechanover received the Nobel Prize in Chemistry “for the discovery of ubiquitin-mediated protein degradation” (Nobel Prize, 2004). The three worked together during the 1970s, 80s, and 90s to define the degradation of proteins within cells via the protein ubiquitin ligase and its associated enzymes. Hershko specifically carried out much of the research outlining the role of ubiquitin mediated degradation of cyclin and its importance in the cell cycle.

The MBL played a key role in much of the early work on the cell cycle, starting with Joan Ruderman and her initial work with clam embryos. The summer research program at the MBL allowed her to add Tim Hunt to the investigation, leading to his later discovery of cyclin in sea urchins. The Friday evening lectures fostered a relationship between Hunt and John Gerhart and his team, including two other MBL researchers, Marc Kirschner and Andrew Murray. Gerhart and his team began much of the work with MPF and the cell cycle, which helped to molecularly explain the genetic phenomena seen by Paul Nurse and Lee Hartwell. And finally, the MBL allowed Avram Hershko to work with the same clam embryos Ruderman worked with to conduct his research on the degradation of cyclin.

Suggested citation
Abboud, Alexis. 2015. "Cyclins at the MBL". MBL History Project digital exhibit. http://history.archives.mbl.edu/exploring/exhibits/cyclins-mbl
Bibliography

What are Cyclins?

Early Work with Cyclins

Tim Hunt and His Discovery of Cyclin

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  • Gerhart, J., Wu, M., & Kirschner, M. (1984). Cell cycle dynamics of an M-phase-specific cytoplasmic factor in Xenopus laevis oocytes and eggs. The Journal of Cell Biology, 98(4), 1247-1255.
  • Hunt, T. (2001, December 9). Tim Hunt Nobel Lecture Protein Synthesis, Proteolysis, and Cell Cycle Transitions." Nobelprize.org. Retrieved from: http://www.nobelprize.org/nobel_prizes/medicine/laureates/2001/hunt-lecture.html
  • Hunt, T. (2004). The Discovery of Cyclin (I). Cell, S116, S63-S64.
  • Jackson, P.K. (2008). The Hunt for Cyclin. Cell, 134, 199-202
  • Masui, Yoshio, and Clement L. Markert. "Cytoplasmic control of nuclear behavior during meiotic maturation of frog oocytes." Journal of Experimental Zoology Part A: Ecological Genetics and Physiology 177, no. 2 (1971): 129-145.
  • Pulverer, B. (2002). http://www.nature.com/celldivision/milestones/full/milestone12.html
  • Swenson, K. I., Farrell, K. M., & Ruderman, J. V. (1986). The clam embryo protein cyclin A induces entry into M phase and the resumption of meiosis in Xenopus oocytes. Cell, 47(6), 861-870.

Cyclins and Genetics

  • Ciechanover, A., Finley, D., & Varshavsky, A. (1984). Ubiquitin dependence of selective protein degradation demonstrated in the mammalian cell cycle mutant ts85. Cell, 37(1), 57-66.
  • Glotzer, M., Murray, A. W., & Kirschner, M. W. (1991). Cyclin is degraded by the ubiquitin pathway. Nature, 349(6305), 132-138.
  • Goldstein, G., Scheid, M., Hammerling, U., Schlesinger, D. H., Niall, H. D., & Boyse, E. A. (1975). Isolation of a polypeptide that has lymphocyte-differentiating properties and is probably represented universally in living cells. Proceedings of the National Academy of Sciences, 72(1), 11-15.
  • Gould, K. L. & Nurse, P. (1991). Tyrosine phosphorylation of the fission yeast cdc2+ protein kinase regulates entry into mitosis. Nature 342, 39-45.
  • Greenwood, E. (2002). http://www.nature.com/celldivision/milestones/full/milestone09.html
  • Hartwell, L. H., Culotti, J., Pringle, J. R., & Reid, B. J. (1974). Genetic control of the cell division cycle in yeast. Science, 183(4120), 46-51.
  • Hershko, A. (1991). The ubiquitin pathway for protein degradation. Trends in biochemical sciences, 16, 265-268.
  • Hershko, A. (1999). Mechanisms and regulation of the degradation of cyclin B. Philosophical Transactions of the Royal Society B: Biological Sciences, 354(1389), 1571-1576.
  • Nature. (2004). A prize for protein degradation. Nature Cell Biology, 6(1011), doi:10.1038/ncb1104-1011.
  • Nobel Prize 2001 http://www.nobelprize.org/nobel_prizes/medicine/laureates/2001/
  • Nobel Prize 2004 http://www.nobelprize.org/nobel_prizes/chemistry/laureates/2004/ ; http://www.nobelprize.org/nobel_prizes/chemistry/laureates/2004/hershko-bio.html
  • Nurse, P. (1975). Genetic control of cell size at cell division in yeast. Nature, 256, 547-551.
  • Nurse, P., & Thuriaux, P. (1980). Regulatory genes controlling mitosis in the fission yeast Schizosaccharomyces pombe. Genetics, 96(3), 627-637.
  • Patterson, M. (2002). http://www.nature.com/celldivision/milestones/full/milestone05.html
  • Russell, P. & Nurse, P. (1986). cdc25+ functions as an inducer in the mitotic control of fission yeast. Cell 45, 145-153.
  • Schoenheimer, R. (1942). The Dynamic State of Body Constitutents. Cambridge: Harvard University Press.
  • Varshavsky, A. (2006). The early history of the ubiquitin field. Protein science, 15(3), 647-654.